Screening practices of cancer survivors and individuals whose family or friends had a cancer diagnoses-a nationally representative cross-sectional survey in Japan (INFORM Study 2020).

PURPOSE: We examined cancer screening practices and related beliefs in cancer survivors and individuals with family or close friends with a cancer diagnosis compared to individuals without the above cancer history for 5 population-based (gastric, colorectal, lung, breast, cervical) and 1 opportunistic (prostate) cancer screenings using nationally representative cross-sectional survey in Japan. METHODS: We analyzed 3269 data from 3605 respondents (response rate, 37.1%) and compared the screening beliefs and practices of cancer survivors (n = 391), individuals with family members (n = 1674), and close friends with a cancer diagnosis (n = 685) to those without any cancer history (n = 519). RESULTS: Being a cancer survivor was associated with screening for gastric (OR, 1.75; 95% CI, 1.04-2.95), colorectal (OR, 1.56; 95% CI, 1.03-2.36), and lung cancer (OR, 1.71; 95% CI, 1.10-2.66) but not breast, cervical cancer or PSA test. Having a family cancer diagnosis was associated with colorectal and lung cancer screening. Having friends with a cancer diagnosis was associated with PSA test. Cancer survivors and family members perceived themselves as being more susceptible and worried about getting cancer than individuals without any cancer history. Cancer survivors strongly believed screening can detect cancer and were more likely to undergo screening. Subgroup analysis indicated an interrelation between gastric and colorectal cancer screening among survivors. CONCLUSIONS: A cancer diagnosis in oneself or family or friend influences an individual's health-related belief and risk perception, which can increase the likelihood of cancer screening. IMPLICATIONS FOR CANCER SURVIVORS: Targeted and tailored communication strategies can increase awareness of cancer screening.

Eosinophilic granuloma with Splendore-Hoeppli material caused by Mannheimia granulomatis in a calf.

A large subcutaneous mass, formed on the left lower jaw of a 4-month-old Japanese Black male calf, was partially excised for histological and bacteriological examinations. Antibiotic treatment resulted in a good prognosis. Bacteria isolated from the excised material were characterized by weak hemolysis and positive reactions for catalase and oxidase, and were 99% identical to Mannheimia granulomatis strains. The presence of the leukotoxin gene product was demonstrated by polymerase chain reaction amplification. Histological examination showed that the excised material was composed of dense fibrous connective tissue with sparsely distributed eosinophilic granulomas or abscesses. These foci frequently contained Splendore-Hoeppli material with rod-shaped Gram-negative bacteria. Except for the absence of lymphangitis and the presence of basophils and mast cells, the histology of this lesion resembled that of lechiguana associated with coinfection of M. granulomatis and Dermatobia hominis. Leukotoxin was demonstrated by immunohistochemistry within Splendore-Hoeppli material and was judged to be responsible for its formation.

Characterization of a novel plasmid, pMAH135, from Mycobacterium avium subsp. hominissuis.

Mycobacterium avium complex (MAC) causes mainly two types of disease. The first is disseminated disease in immunocompromised hosts, such as individuals infected by human immunodeficiency virus (HIV). The second is pulmonary disease in individuals without systemic immunosuppression, and the incidence of this type is increasing worldwide. M. avium subsp. hominissuis, a component of MAC, causes infection in pigs as well as in humans. Many aspects of the different modes of M. avium infection and its host specificity remain unclear. Here, we report the characteristics and complete sequence of a novel plasmid, designated pMAH135, derived from M. avium strain TH135 in an HIV-negative patient with pulmonary MAC disease. The pMAH135 plasmid consists of 194,711 nucleotides with an average G + C content of 66.5% and encodes 164 coding sequences (CDSs). This plasmid was unique in terms of its homology to other mycobacterial plasmids. Interestingly, it contains CDSs with sequence homology to mycobactin biosynthesis proteins and type VII secretion system-related proteins, which are involved in the pathogenicity of mycobacteria. It also contains putative conserved domains of the multidrug efflux transporter. Screening of isolates from humans and pigs for genes located on pMAH135 revealed that the detection rate of these genes was higher in clinical isolates from pulmonary MAC disease patients than in those from HIV-positive patients, whereas the genes were almost entirely absent in isolates from pigs. Moreover, variable number tandem repeats typing analysis showed that isolates carrying pMAH135 genes are grouped in a specific cluster. Collectively, the pMAH135 plasmid contains genes associated with M. avium's pathogenicity and resistance to antimicrobial agents. The results of this study suggest that pMAH135 influence not only the pathological manifestations of MAC disease, but also the host specificity of MAC infection.

Comparative genome analysis of Mycobacterium avium revealed genetic diversity in strains that cause pulmonary and disseminated disease.

Mycobacterium avium complex (MAC) infection causes disseminated disease in immunocompromised hosts, such as human immunodeficiency virus (HIV)-positive patients, and pulmonary disease in persons without systemic immunosuppression, which has been increasing in many countries. In Japan, the incidence of pulmonary MAC disease caused by M. avium is about 7 times higher than that caused by M. intracellulare. To explore the bacterial factors that affect the pathological state of MAC disease caused by M. avium, we determined the complete genome sequence of the previously unreported M. avium subsp. hominissuis strain TH135 isolated from a HIV-negative patient with pulmonary MAC disease and compared it with the known genomic sequence of M. avium strain 104 derived from an acquired immunodeficiency syndrome patient with MAC disease. The genome of strain TH135 consists of a 4,951,217-bp circular chromosome with 4,636 coding sequences. Comparative analysis revealed that 4,012 genes are shared between the two strains, and strains TH135 and 104 have 624 and 1,108 unique genes, respectively. Many strain-specific regions including virulence-associated genes were found in genomes of both strains, and except for some regions, the G+C content in the specific regions was low compared with the mean G+C content of the corresponding chromosome. Screening of clinical isolates for genes located in the strain-specific regions revealed that the detection rates of strain TH135-specific genes were relatively high in specimens isolated from pulmonary MAC disease patients, while, those of strain 104-specific genes were relatively high in those from HIV-positive patients. Collectively, M. avium strains that cause pulmonary and disseminated disease possess genetically distinct features, and it suggests that the acquisition of specific genes during strain evolution has played an important role in the pathological manifestations of MAC disease.

[Identification of novel variable number tandem repeat (VNTR) loci in Mycobacterium avium and development of an effective means of VNTR typing].

INTRODUCTION: To make more effective use of variable number tandem repeat (VNTR) typing, we identified novel VNTR loci in Mycobacterium avium and used them for modified M. avium tandem repeat-VNTR (MATR-VNTR) typing. METHOD: Analysis of a DNA sample extracted from a clinical isolate (strain HN135) with the FLX system genome sequencer (Roche Diagnostic System) led to discovery of several novel VNTR loci. The allelic diversity of the novel VNTR loci was evaluated for 71 clinical isolates and compared with the diversity of the MATR-VNTR loci. To improve efficacy of MATR-VNTR typing, we tested typing using 2 sets of loci selected from the newly identified loci and the MATR loci, i.e., one set containing 7 and another 16 loci. Hunter Gaston's discriminatory index (HGDI) was calculated for these sets. RESULTS: Six VNTR loci were newly identified, of which 5 showed a high diversity. The HGDI was 0.980 for the improved new typing using a set of 7 loci, and 0.995 for another set of 16 loci, while it was 0.992 for the conventional MATR-VNTR typing. DISCUSSION: VNTR typing with the set of the 7 loci enabled a rapid analysis, and another set of 16 loci enabled a precise analysis, as compared with conventional MATR-VNTR typing. A method that uses only VNTR loci with relatively high allelic diversity is considered to be a useful tool for VNTR typing of MAC isolates.

[A study of genetic characteristics of Mycobacterium avium strains from patients with pulmonary M. avium disease in Japan and Korea].

INTRODUCTION: To determine the characteristics of Mycobacterium avium in Japan, we compared the genetic properties of M. avium isolated in different countries. METHODS: A Mycobacterium avium tandem-repeat variable-number tandem-repeat (MATR-VNTR) analysis was performed using South Korean strains (n = 119) and Japanese strains (n = 76). In addition, we compared the frequencies of a new insertion sequence, ISMav6. RESULTS: A phylogenetic analysis identified different clusters between the two countries' strains. The prevalence of ISMav6 was significantly different between them, i.e., 75.0% in Japanese strains and 59.8% in the Korean ones (P < 0.035). The frequency of strains with IS Mav6 in the Shine-Dalgarno (SD) sequence of the cfp29 gene that is involved in the interferon-gamma induction was also different, with stronger significance (Japan: 38.2%, Korea: 12.4%, P < 0.001). DISCUSSION: It is possible that M. avium strains prevalent in Japan and in Korea are genetically distinct. The analyses of the presence of ISMav6, as well as the VNTR patterns of M.avium strains from many different countries would be a promising methodology in elucidating the causes of the recent increase in cases of pulmonary MAC diseases.

[Multicenter study on clinical features and genetic characteristics of Mycobacterium avium strains from patients in Japan with lung disease caused by M. avium].

BACKGROUND: The pulmonary disease caused by Mycobacterium avium shows diverse clinical manifestations. Little is known about the potential association between the genetic characteristics of M. avium strains and disease progression. SUBJECTS AND METHODS: We enrolled 89 patients with disease caused by M. avium, from 12 hospitals in Japan and collected the corresponding M. avium isolates and clinical data. We divided the 89 patients into 2 groups: one group comprising 43 patients with progressive disease despite chemotherapy ("progressive"), and the other group comprising 46 patients with untreated disease ("untreated"). We compared clinical and bacteriological characteristics between these groups. The bacteriological characteristics that we examined were drug susceptibility, variable-number tandem-repeat (VNTR) typing, and presence of the insertion sequence ISMav6. Seventeen patients in the "untreated" group were started on chemotherapy because their condition had clinically deteriorated during follow-up. RESULTS: The result of VNTR typing showed that there was no specific clustering according to geographical region or clinical group in the "untreated" or "progressive" groups. Six out of eight cases those of polyclonal infection, and 11 of 12 isolates that were highly resistant to clarithromycin were isolated from patients with progressive disease. The frequency of isolates with ISMav6 inserted into upstream region of the cfp29 gene, which is involved in the induction of interferon-gamma production, was significantly higher in patients with deteriorating disease than in stable patients in the "untreated" group (p = 0.002). CONCLUSION: Polyclonal infection and clarithromycin resistance may be involved in disease progression. ISMav6 inserted into the cfp29 gene is also suggested to be a factor related to the deterioration of pulmonary Mycobacterium avium complex disease.

Novel dihydrothieno[2,3-e]indazole derivatives as IκB kinase inhibitors.

Synthesis, and structure-activity relationship (SAR) studies of the novel IKK-ß inhibitors 2 and 3 characterized by a dihydrothieno[2,3-e]indazole core are presented. Compound 2t was efficacious in a mouse model of LPS-stimulated TNF-α production.